ADT increased risk for diabetes, fractures in elderly men with recurrent prostate cancer

Should ADT only be one part of an overall chronic disease management strategy?

Elderly men with prostate cancer undergoing androgen deprivation therapy were at increased risk for diabetes and fragility fractures, but not acute myocardial infarction or sudden cardiac death, according to the results of a Canadian study.

William Dale, MD, PhD, assistant professor of medicine and chief of geriatrics and palliative medicine at the University of Chicago, wrote in an accompanying editorial that such findings show that in addition to staging and grading the cancer, physicians need to “stage and grade the aging” to ensure that cancer treatments work in concert with the overall care of all older cancer patients.

“Therapies need to be considered in all their effects, not just those on the cancer itself,” Dale told HemOnc Today. “Up to this point, at least with ADT, we’ve said it’s okay to accept the known quality of life decrement associated with the therapy because it’s extending patient’s lives who have widely metastatic cancer. But when you start to read the geriatrics literature on frailty and recognize ADT is causing frailty in asymptomatic older men with minimal cancer burden, you realize making people frail not only lowers their quality of life it might also be life threatening itself.”

In the study, published in a recent issue of The Journal of Clinical Oncology, Shabbir M.H. Alibhai, MD, and colleagues conducted a matched cohort study that identified 116,769 men aged 66 or older with prostate cancer from the Ontario Cancer Registry. From that population, the researchers selected 24,518 men who had received androgen deprivation therapy and met the study criteria. Those men were matched with 19,079 men who had not undergone ADT.

Contrary to some prior research, the researchers found that ADT use was not associated with increased risk for myocardial infarction (HR=0.92; 95% CI, 0.84-1.00) or sudden cardiac death (HR=0.96; 95% CI, 0.83-1.10). However, rates of diabetes incidence were higher in patients assigned ADT compared with those who were not (7.1% vs. 6.0%; HR=1.26; 95% CI, 1.16-1.36).

Secondary outcomes

Nine percent of the ADT group had a fragility fracture compared with 5.9% of the non-ADT group (HR=1.65; 95% CI, 1.53-1.78). When evaluating any fracture, 17.2% of the ADT group sustained a fracture compared with 12.7% of the non-ADT group (HR=1.46; 95% CI, 1.39-1.54).

“If you have low-grade (ie, low-Gleason score) prostate cancer, several other significant diseases, and disability, I don’t think you should start on this therapy. It’s too dangerous,” Dale said. “If you’re a young person with high-grade prostate cancer and a PSA that’s rising rapidly, I think it makes good sense to treat the cancer with ADT. We need to put the decision into context for the patients: For example, if you are going to start a patient on ADT, their likelihood of developing diabetes goes up approximately 30%, according to this study. That should be a consideration in making this decision.

“For older patients, you have to be especially careful when you start this therapy, especially if you’re starting it for older patients who are otherwise asymptomatic from their cancer. You’re going to lower their quality of life and if you’re not going to extend their life, it’s hard to justify starting therapy right away,” Dale said.

The researchers also paradoxically found that ADT use was associated with a reduced risk for stroke (HR=0.88; 95% CI, 0.81-0.96). Only 5.4% of those on the therapy had a stroke compared with 6.5% of nonusers. They determined that the finding was “best viewed as hypothesis-generating” and needed further confirmation, but said that cardiovascular disease develops over years and decades so these conditions might become more prevalent over time.

Follow-up vital

In his accompanying editorial, Dale argued that patients starting ADT tend to visit a physician more often than those who do not. This is because getting ADT requires an injection in the doctor’s office every three to four months. A physician would therefore have more opportunities to notice a condition such as rising blood pressure or new diabetes that are risk factors for strokes and treat the patient accordingly. Those not on ADT likely visit physicians less often and have less opportunity to have these conditions managed.

Dale stressed that ADT should be used as only one part of an overall disease management strategy for older men, especially when dealing with low-volume, low-grade prostate cancer. Use of the treatment, he wrote in his editorial, should be integrated into an overall treatment approach that accounts for life expectancy, comorbidities and functional losses. – by Jason Harris

Alibhai SMH. J Clin Oncol. 2009;doi:10.1200/JCO.2008.20.0923.

Dale W. J Clin Oncol. 2009;doi:10.1200/JCO.2009.22.9104.